In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine
In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine
复制标题
含别苯基去甲他汀的过渡态模拟 HIV 蛋白酶抑制剂的体外抗人类免疫缺陷病毒 (HIV) 活性
DOI：
--
复制
发表时间：
1993
影响因子：
4.9
通讯作者：
H. Hayashi
中科院分区：
文献类型：
--
作者：
S. Kageyama;T. Mimoto;Y. Murakawa;M. Nomizu;H. Ford;T. Shirasaka;S. Gulnik;J. Erickson;K. Takada;H. Hayashi
Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in target CD4+ ATH8 cells, the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively. Both agents completely blocked the replication of 3'-azido-2',3'-dideoxythymidine-sensitive and -insensitive clinical HIV-1 isolates at 0.08 microM as tested in target phytohemagglutinin-activated peripheral blood mononuclear cells. The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI-272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells. Both compounds blocked the posttranslational cleavage of the p55 precursor protein to generate the mature p24 Gag protein in stably HIV-1-infected cells. The n-octanol-water partition coefficients of KNI-227 and KNI-272 were high, with log Po/w values of 3.79 and 3.56, respectively. Degradation of KNI-227 and KNI-272 in the presence of pepsin (1 mg/ml, pH 2.2) at 37 degrees C for 24 h was negligible. Current data warrant further careful investigations toward possible clinical application of these two novel compounds.
影响因子：
56.9
作者：
ERICKSON, J;NEIDHART, DJ;KNIGGE, M
通讯作者：
KNIGGE, M
DOI：
10.1073/pnas.88.24.11241
发表时间：
1991-12
影响因子：
11.1
作者：
D. Richman;C. Shih;Israel Lowy;J. Rose;Patricia C. Prodanovich;S. Goff;J. Griffin
通讯作者：
D. Richman;C. Shih;Israel Lowy;J. Rose;Patricia C. Prodanovich;S. Goff;J. Griffin
p17/p24 底物裂解位点的羟乙胺类似物是 HIV 蛋白酶的紧密结合抑制剂。
影响因子：
7.3
作者：
Rich,DH;Green,J;Toth,MV;Marshall,GR;Kent,SB
通讯作者：
Kent,SB